Dementia and Neurocognitive Disorders 2011; 10: ORIGINAL ARTICLE 주의력설문지척도 (Attention Questionnaire Scale) 를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력

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1 Dementia and Neurocognitive Disorders 2011; 10: ORIGINAL ARTICLE 주의력설문지척도 (Attention Questionnaire Scale) 를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 구본대 * 김상윤 관동대학교의과대학명지병원신경과 *, 서울대학교의과대학신경과학교실분당서울대학교병원신경과 Received: June 26, 2010 Revision received: September 19, 2011 Accepted: September 19, 2011 Address for correspondence SangYun Kim, M.D. Department of Neurology, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam , Korea Tel: Fax: neuroksy@snu.ac.kr *This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). * 본연구는 2009 년대한치매학회얀센학술상의연구비지원에의해이루어진것임. Attentional Differences according to the Subcortical White Matter Hyperintensities in Patients with Alzheimer Disease and Subcortical Vascular Dementia using Attention Questionnaire Scale Bon D. Ku, M.D.*, SangYun Kim, M.D. Department of Neurology*, Myongji Hospital, Kwandong University College of Medicine, Goyang; Department of Neurology, Seoul National University Bundang Hospital & Seoul National University College of Medicine, Seongnam, Korea Background: Attention is too difficult to measure quantification due to the numerous affected variables. Attention Questionnaire Scale (AQS) is a newly developed scale for the evaluation of the patient s attention. The aim of this study was to adapt AQS to evaluate the correlation between attention and subcortical hyperintensities (SH) to the patients with mild to moderate Alzheimer disease (AD) or subcortical vascular dementia (SVD). Methods: Patients with mild to moderate AD or SVD were recruited from March 2008 to February On magnetic resonance imaging, deep white matter (DWM) hyperintensities were classified into D1 (the longest diameter of DWM lesion < 10 mm), D2 (10 mm DWM 24 mm), and D3 (25 mm < DWM). Likewise, periventricular white matter (PWM) hyperintensities were classified into P1 (caps or rim < 5 mm), P2 (between P1 and P2), and P3 (10 mm < caps or rim). The SH was divided into three groups according to the combinations of DWM and PWM hyperintensities: minimal (D1P1, D1P2, D2P1), severe (D3P3), and moderate hyperintensities group with hyperintensities of remaining combinations. AQS, Korean version of Mini-Mental Status Examination (K-MMSE), Clinical Dementia Rating (CDR) and Global Deterioration Scale (GDS) were performed in all the patients. Patients with mild to moderate AD or SVD were divided into three groups according to the SH (minimal, moderate and severe SH group). We evaluate AQS, K-MMSE, CDR and GDS according to the degree of SH. Results: A total of 162 study patients were recruited (87 in minimal, 22 in moderate and 53 in severe SH group). Female was predominant in all three groups (66.7%). Mean score of K-MMSE was 17.5± 5.7 and that of the CDR was 1.3± 0.9. Mean score of AQS was 17.1± 7.9. The correlation between AQS and other scales such as K-MMSE, CDR and GDS were all significant (the correlation coefficiency was 0,317, , , respectively). Unlike other scales AQS showed significant differences between minimal and moderate or severe SH group (18.7± 7.7, 15.2± 6.6, 15.4± 8.6, p = 0.007). Conclusions: AQS is a useful dementia scale for the evaluation of the degree of SH in the patients with mild to moderate AD or SVD. Key Words: Alzheimer disease, Subcortical vascular dementia, Attention Questionnaire Scale, Subcortical hyperintensities 서론주의력 (attention) 은지각을조절하는기본적인지기능으로외부환경이나개체로부터의자극을인지하고반응하는정보선택및처리의과정이다 [1]. 주의력은제한된뇌자원의선택적분배를가능하게하여생체의정보처리능력을효율화시키는역할을하며다른인지기능에많은영향을미친다 [1, 2]. 주의력은주의-집중력이라고 표현하기도하는데주의력은무의식적으로수행되는부분에중점을둔표현이고집중력은의식적인부분에중점을둔표현이다 [2, 3]. 그러나실제임상에서주의력과집중력을명확히구분하기는어려워주의-집중력이라는용어로사용되는경우가많다 [1, 3]. 주의력에관계되는대표적인뇌구조물에는망상활성체계 (reticular activating system), 중뇌상구 (superior colliculi of midbrain), 시상, 두정엽, 전대상피질, 전두엽등이있다. 망상활성체계의피질상향조 80

2 주의력설문지척도를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 81 정 (bottom-up) 은각성상태를유지하는역할을하고변연계두정엽특히전전두엽등은하향조정 (top-down) 을통하여외부자극을선택하고인지하게하는역할을한다 [1]. 따라서주의력의손상은치매환자에서기억력을비롯한다른인지영역에영향을주게되고더나아가환자의일상생활능력을저하시키는원인이되기도한다 [2]. 그러나인지장애의원인질환이나중등도에따라주의력저하의정도와유형에차이가있어기존의외상성뇌손상, 정신분열증, 만성피로증후군환자를대상으로만들어진 Brock Adaptive Functioning Questionnaire [4], Dysexecutive Questionnaire [5], Everyday Attention Questionnaire [6] 등을치매환자에게적용하기에는어려움이있다. 또알츠하이머병 (Alzheimer disease, AD) 환자는기억부담이큰주의배분이나주의전환이요구되는선택적주의력이초기부터저하되고지속적주의력은상대적으로유지되는경향을보인다 [1,7]. 반면에피질하혈관성치매 (subcortical vascular dementia, SVD) 환자는전두-피질하연결 (frontal-subcortical circuit) 의장애로기억력이나언어능력보다는전두엽장애가두드러져 AD에비하여지속적주의력의손상이초기부터나타나는경향이있다 [1, 8]. 이러한점에서주의력설문지척도 (Attention Questionnaire Scale, AQS) 는치매환자의주의력측정에초점을두고제작된설문이라는장점이있다 [9]. 본연구는 AD 및 SVD 환자에서피질하고신호병변 (subcortical hyperintensities) 의정도가주의집중력에미치는영향에대하여알아보고자하였다. 임상적으로 AD와 SVD로진단된환자군을대상으로 Korean-mini-mental status examination (K-MMSE), clinical dementia rating (CDR), global deterioration scale (GDS) 와 AQS 를시행하고 AQS와 K-MMSE, CDR, GDS 사이의상관성을살펴보아피질하고신호병변의정도에따른 AQS, K-MMAE, CDR, GDS의차이를조사하였다. 대상과방법 1. 대상 대상자에게검사의목적을충분히설명한후에서면동의서를받았다. 환자중내과적신경과적, 정신과적으로치매와는별도로질병자체가인지기능에영향을줄수있는환자, 임상연구에서요구하는사항들의수행에지장을줄수있는장애가있는환자는배제하였다. 2. 방법인지기능평가는보호자문진을먼저하고환자에게기억력, 언어능력, 시공간능력, 주의력및계산능력, 판단력, 문제해결능력, 추상적사고등을포함하는문진을하였다. 문진후에 K-MMSE, CDR, GDS 및뇌자기공명영상 (magnetic resonance imaging, MRI: T1 axial, T2 axial, FLAIR axial, T1 coronal 및 gradient echo axial) 을실시하였다치매의원인질환을감별하기위하여비타민 B12, 엽산, 갑상선기능검사, 매독반응검사를실시하였다. 1) AQS AQS는주의력의유형을집중 (focused), 지속 (sustained), 선택 (selective), 배분 (divided) 및교대 (alternating) 주의력으로구분하여환자의상태를잘아는보호자가환자의주의력의여러부분을평가하여환자의주의력에대한정보를제공하는설문지이다 [9]. 검사는모두 15개의설문으로이루어졌고각각의설문에대하여 전혀그렇지않다 (0점), 가끔또는조금그렇다 (1점 ), 항상또는많이그렇다 (2점 ) 중에 1개를선택하도록구성되었다. 1번부터 8점까지의설문은환자의주의력이떨어질수록높은점수를주도록구성되었고 (AQS1), 9번부터 15번까지는환자의주의력이높을수록높은점수를주도록구성되어있다 (AQS2). 평가점수는 16-AQS1+AQS2 로계산하여환자의주의력을점수화하였다 (Appendix). 따라서환자의주의력은 0-30점의점수로환산되며환자의집중력이높을수록높은점수를기록하게된다 [9]. AQS는 1주일에 2회이상환자와함께있어환자의증상에대해말해줄수있는보호자 1인이상에의하여평가하였다. 일부요양원이나장기요양기관에서간병서비스를받는경우에는보호자와간병인이함께평가하도록하였다. 본연구에포함된환자는 2008년 3월부터 2010 년 2월까지인지장애및치매클리닉에내원한환자중 National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association 기준 [10] 과 National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l Enseignement en Neurosciences 기준 [11] 에따라경증에서중등도의 AD와 SVD로진단된환자를대상으로하였다. 본연구는연구윤리위원회의승인을받았으며, 연구에참여하는모든 2) 뇌영상백질고신호병변의평가는보건복지부지정노인성치매임상연구센터의백질고신호병변기준에따라실시하였다 ( Philips Gyroscan Intera 1.5 Tesla Nova Dual MRI (Philips Electronics, Eindhoven, Netherlands) 기종을사용하여 T1-weighted (TR/TE 450/12 msec,flip angle 69, thickness 6 mm), T2-weighted (TR/TE 40200/100 msec, flip angle 90, thickness 6 mm), FLAIR (TR/TE 11,000/140, flip angle 90, thickness 6 mm ), Gradient echo (TR/TE 63/23, flip angle 18

82 구본대 김상윤 thickness 6 mm) 횡단영상을얻었고 T1 coronal (TR/TE 450/12, flip angle 69, thickness 6 mm ) 영상을얻었다.

우선 DWM을기준으로피질하고신호병변의방향에관계없이가장긴직경을기준으로 D1: 10 mm 미만, D2: 10-24 mm 사이, D3: 25 mm 이상으로나누었다. DWM을 PVWM과구분하기위하여뇌실가쪽벽쪽 (lateral side) 으로정상백질이존재하여야하며마지막뇌실이보인 MRI의두번째상방영상부터측정하였다.

Capping과 banding 모두 5 mm 미만인경우 P1, 둘중하나라도 10 mm 이상인경우엔 P3, 그사이는모두 P2로정하였다 (Fig. 1).

3 82 구본대 김상윤 thickness 6 mm) 횡단영상을얻었고 T1 coronal (TR/TE 450/12, flip angle 69, thickness 6 mm ) 영상을얻었다. MRI 상에서관찰되는피질하고신호병변의정도는열공성뇌경색병변 (lacunar infarction lesion) 은고려하지않고뇌실주변백질 (periventricular white matter, PVWM) 과심부백질 (deep white matter, DWM) 을기준으로하였다. 우선 DWM을기준으로피질하고신호병변의방향에관계없이가장긴직경을기준으로 D1: 10 mm 미만, D2: mm 사이, D3: 25 mm 이상으로나누었다. DWM을 PVWM과구분하기위하여뇌실가쪽벽쪽 (lateral side) 으로정상백질이존재하여야하며마지막뇌실이보인 MRI의두번째상방영상부터측정하였다. PVWM은 capping과 banding으로측정하였는데 capping은뇌실에직각방향 (vertical axis) 으로, banding 은뇌실과수평방향 (horizontal axis) 으로가장큰직경 (diameter) 을측정하였다. Capping과 banding 모두 5 mm 미만인경우 P1, 둘중하나라도 10 mm 이상인경우엔 P3, 그사이는모두 P2로정하였다 (Fig. 1). D와 P를조합하여최소피질하고신호병변군 (minimal subcortical hyperintensities; D1- P1, D1-P2, D1-P3, D2-P1), 중등도피질하고신호병변군 (moderate subcortical hyperintensities; D2-P2, D2-P3, D3-P1, D3-P2), 중증의피질하고신호병변군 (severe subcortical hyperintensities; D3-P3) 으로구분하였다 (Table 1). 3. 통계분석 AD와 SVD 두군간비교는 student-t test 및 chi-square 분석을하였으며피질하고신호병변에따른세군간의분석은 analysis of variance 분석을시행하였고 Post hoc 분석은 Scheffe correction 을시행하 였다. AQS 와 K-MMSE, CDR 및 GDS 사이의상관정도는 Pearson correlation 을시행하였다. 본연구의자료분석을위한통계적검증은 SPSS 13.0 version 을이용하였으며유의성은 p < 0.05 이하로하였다. 1. 인구학적변인 결과 연구기간동안 AD 혹은 SVD 로진단된환자는 162 명이었고, 그 중 AD 가 118 명 (72.8%) 이었다. 162 명중최소, 중등도, 중증의피질하 고신호병변군은각각 87 명, 22 명, 53 명이었다. AD 로진단된 118 명의 환자를피질하고신호병변에따라분류하면최소, 중등도, 중증의 피질하고신호병변군이각각 87 명, 22 명, 9 명이었고 SVD 환자 44 명 은모두중증의피질하고신호병변군이었다. 162 명의평균나이는 74.9 ± 7.8 세였으며여성환자가 110 명으로전체환자의 68.0% 를차지 하였다. 두집단의인구학적변인에서연령, 성비, 손잡이, 교육연수, Table 1. Definition of the degree of subcortical hyperintensities D1 ( < 10 mm) D2 (10-24 mm) D3 ( 25 mm) P1 ( < 5mm in capping Minimal Minimal Moderate and banding) P2 (between P1 and P2) Minimal Moderate Moderate P3 ( > 10 mm in capping or banding) Minimal Moderate Severe P, Periventricular white matter; D, Deep white matter. A P1: caps<5 mm P2: 5 mm caps<10 mm P3: caps 10 mm P1: bands<5 mm P2: 5mm bands <10 mm P3: bands 10 mm B C D D1: DWML at ventricle < 10 mm D2: 10mm DWML at ventricle < 24 mm D3: DWML at ventricle 25 mm D1: DWML at semiovale < 10 mm D2: 10mm DWML at semiovale <24 mm D3: DWML at semiovale 25 mm Fig. 1. The examples of the periventricular white matter hyperintensities of frontal and occipital horn (A), periventricular white matter hyperintensities along the lateral ventricle (B), deep white matter hyperintensities of lateral ventricle level (C) and deep white matter hyperintensities of centrum semiovale level (D).

주의력설문지척도를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 83 질병유병기간, 키, 몸무게, 체질량지수에서유의한차이는없었다 (Table 2). 2. 전반적인지기능및치매중등도 전체환자집단의평균 K-MMSE 는 17.5 ± 5.7, CDR 은 1.3± 0.9, GDS 는 4.1± 1.1 이었다.

4 주의력설문지척도를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 83 질병유병기간, 키, 몸무게, 체질량지수에서유의한차이는없었다 (Table 2). 2. 전반적인지기능및치매중등도 전체환자집단의평균 K-MMSE 는 17.5 ± 5.7, CDR 은 1.3± 0.9, GDS 는 4.1± 1.1 이었다. AD 환자집단의평균 K-MMSE 는 16.8± 5.9, CDR 은 1.4±1.0, GDS 는 4.2±1.1 이었고, SVD 환자집단의 K-MMSE 는 17.0± 5.4, CDR 은 1.4 ± 0.9, GDS 는 4.2 ± 1.1 으로두군사이의전반적인지기 능및치매중등도의차이는없었다 (Table 2). 3. 주의력설문지척도 전체집단의 AQS 평균점수는 17.1± 7.9 이었고 AQS1 의평균점수 는 5.7± 4.9 이고 AQS2 의평균점수는 6.9 ± 4.0 이었다. AD 환자집단 에서는 AQS 평균점수는 16.8± 7.6 이었으며 AQ1 의평균점수는 5.9 ± 4.6 이고 AQ2 의평균점수는 6.7± 4.1 이었다. SVD 환자집단의 AQS 평 균점수는 15.8± 8.9 으로 AQS1 의평균점수는 6.9 ± 6.0 이고 AQS2 의 평균점수는 6.6 ± 3.9 이었다 AD 환자와 SVD 환자집단간의 AQS 및 AQS1 과 AQS2 의평균점수에서유의한차이는없었다 (Table 2). 4. 전반적인지기능및치매중등도와 AQS 의상관정도 AQS 는인지기능이저하될수록치매가중등도로갈수록유의하 Table 2. The demographic characteristics, general cognitive profiles and Attention Questionnaire Scale of the patients with Alzheimer s disease or subcortical vascular dementia AD (n=118) SVD (n=44) Total (n=162) P-value Age (yr) 75.0± ± ± Gender (M : F) 34 : : : * Hand (R : L : B) 115 : 2 : 1 43 : 1 : : 3 : * Education (yr) 8.11± ± ± Duration (mo) 22.5± ± ± Height (cm) 158.3± ± ± Weight (Kg) 58.5± ± ± K-MMSE 16.8 ± ± ± CDR 1.4 ± ± ± GDS 4.2 ± ± ± AQS 16.8 ± ± ± AQS ± ± ± AQS ± ± ± yr, Year; M, Male; F, Female; Hand, Handedness; R, Right; L, Left; B, Both; mo, Month; BMI, Body mass index; AD, Alzheimer disease; SVD, Subcortical vascular dementia; K-MMSE, Korean mini-mental status examination; CDR, Dementia rating scale; GDS, Global Deterioration Scale; AQS, Attention Questionnaire Scale; AQS-1, AQS gives higher points to the high attention; AQS-2, AQS gives higher points to the low attention; The statistical analysis was done by the T-test, chi-square*. 게높은상관도를보였다 (K-MMSE, γ = 0.317, p < 0.001; CDR, γ = , p < 0.001; GDS, γ-0.472, p < 0.001) (Fig. 2). AD 환자집단은전체집단의 경우와비슷한상관양상을보였지만 (K-MMSE, γ = 0.388, p< 0.001; CDR, γ = , p< 0.001; GDS, γ = , p< 0.001), SVD 환자집단 에서는인지기능저하와는상관성을볼수없었고치매가중등도 로갈때에유의한상관성을보였다. 5. 피질하고신호병변에따른 AQS 의차이 전체환자집단을피질하고신호병변의정도에따라나누었을 때통계적으로세군간의연령차이는없었다. 최소피질하고신호 병변군의평균 AQS 는 18.7±7.7 (AQS1: 4.9± 4.5, AQS2: 7.6± 4.1) 이었 고중등도피질하고신호병변군은평균 AQS 가 15.2 ± 6.6 (AQS1: 6.3 ± 4.6, AQS2: 5.7± 3.6) 이었으며중증의피질하고신호병변군의경우 평균 AQS 가 15.4 ± 8.6 (AQS1: 7.0 ± 5.8, AQS2: 6.5 ± 3.8) 로나타났다. 피 질하고신호병변의정도가증가함에따라 AQS 의평균점수는감 소하는양상이관찰되었다 (p = 0.007). AQS1 은피질하고신호병변 의정도가증가할수록점수가증가하는양상으로나타났고, AQS2 는피질하고신호병변의정도가심해질수록점수가감소하는양상 으로나타났다. Scheffe 사후분석에서 AQS1 의차이는최소와중증 의피질하고신호병변군에서유의하였으며 (p = 0.030), AQS2 에서는 최소와중등도피질하고신호병변에서유의하였다 (p = 0.028). 또한 AQS 의 Scheffe 사후분석결과최소와중등도피질하고신호병변군 (p = 0.045) 및최소와중증의피질하고신호병변군 (p = 0.035) 사이에 서유의한차이가관찰되었다. K-MMSE, CDR, GDS 는피질하고신 호병변증가에따른점수변동의통계적유의성은없었다 (Table 3). The Score of the K-MMSE, CDR or GDS K-MMSE GDS CDR The Score of the Attention Questionnaire Scale Fig. 2. The Pearson correlation between Attention Questionnaire Scale and K-MMSE (γ = 0.317, p < 0.001), CDR (γ = , p < 0.001) or GDS (γ = , p < 0.001). K-MMSE, Korean version of Mini-Mental Status Examination; CDR, Clinical Dementia Rating scale; GDS, Global Deterioration Scale.

5 84 구본대 김상윤 Table 3. Attention Questionnaire Scale and other general cognitive profiles in the patients with Alzheimer disease or subcortical vascular dementia according to the subcortical ischemia Min. HI (n=87) Mod. HI (n=22) Sev. HI(n=53) p value Min. HI- Mod. HI Min. HI- Sev. HI Mod.HI-Sev. HI Age 73.2 ± ± ± AQS 18.7 ± 7.7*, 15.2 ± 6.6* 15.4 ± * AQS ± 4.5* 6.3 ± ± 5.8* * AQs ± 4.1* 5.7 ± 3.6* 6.5 ± * K-MMSE 18.7 ± ± ± CDR 1.2 ± ± ± GDS 4.0 ± ± ± K-MMSE, Korean mini-mental status examination; CDR, Dementia rating scale; GDS, Global Deterioration Scale; AQS, Attention Questionnaire Scale; AQS-1, AQS gives higher points to the high attention; AQS-2, AQS gives higher points to the low attention; AD, Alzheimer disease; SVD, Subcortical vascular dementia. Min. HI, Mod. HI and Sev. HI represent Minimal, moderate and severe subcortical hyperintensities groups respectively. All numerical variables were performed ANOVA with post-hoc analyses representing as mean± standard deviation. p values< 0.05 on comparisons among three groups were italicized. p values< 0.05 by post-hoc analyses were marked and denoted with *between minimal and moderate and between minimal and severe ischemia. 고찰치매환자의대부분을차지하고있는 AD와 SVD는개념상으로는이분법적분류가가능하지만실제임상에서그경계영역을구분하기가어려운경우가많다. 현재까지의임상연구와병인론적연구를종합하면 AD와 SVD는치매라는병리의연속선상의양극단에존재하고있으며, 많은경우가그연속선사이에두가지치매의양상이혼재되어존재한다 [12]. 따라서 AD와 SVD를이분법으로구분하지않고연속선상에서관찰하는것이필요하다. 본연구는경증에서중등도의 AD 및 SVD 환자와보호자를대상으로환자의주의력에대한객관적평가를시도하였다. 그리고피질하고신호병변의정도에따라세개의군으로나누어피질하고신호병변에따른 AQS, K-MMSE, CDR, GDS 등의변동을비교해보았다. MRI에서관찰되는피질하고신호병변은고혈압, 당뇨등의뇌졸중위험인자를가지고있을경우더흔히발견되며인지기능저하와도연관성이높다는연구는정상노인에서치매환자에이르기까지광범위하게이루어졌다 [7, 13-16]. 지역사회거주정상노인을대상으로한장기간추적관찰연구에서도피질하허혈은치매의발병을높이는인자로확인되었으며 [13, 14], 경도인지장애환자에서도 AD로의진행을높이는인자임이보고되었다 [15, 16] 피질하고신호병변의정도에따른평가에서 AQS는 K-MMSE, CDR, GDS 등의척도에비하여피질하고신호병변의정도를민감하게나타났다. 부정질문 (negative question) 으로구성된 AQS1 은최소와중증의피질하고신호병변군에서, 긍정질문 (positive question) 으로구성된 AQS2는중등도와중증의피질하고신호병변군에서유의한차이를보였다. AQS1 과 AQS2를종합한 AQS는최소와중등도및최소와중증의피질하고신호병변군에서의미있는차이를보였다 (Table 2). 통계적유의성을얻지는못하였지만 K-MMSE, GDS 등의척도도피질하고신호병변의증가에따른변동양상을보였다. K-MMSE 는피질하고신호병변이증가할수록점수가감소하는양상을보였고 (p = 0.064) GDS 점수는증가하는양상 (p = 0.069) 을보였는데이는피질하허혈이치매환자의인지기능및중등도를악화시키는요인으로작용함을나타내는것이라고본다 [19]. 본연구에서 AD 환자와비교하여 SVD 환자에서 AQS (p = 0.49) 및 AQS1 (p = 0.37) 과 AQS2 (p = 0.33) 점수는유의한차이를보이지않았다. 그이유는 AQS가 SVD 환자에서주로나타나는지속적주의력장애에대한설문 ( 문항 1, 5, 8, 9, 14, 15) 뿐만아니라 AD환자에서주로나타나는기억력이나시공간능력과관련된선택적주의력혹은주의력배분과관련된장애에대한설문 ( 문항 2, 3, 4, 7) 모두를반영하기때문으로생각된다. 결론적으로, 피질하고신호병변이 AD와 SVD 환자에서치매의중등도에관계없이치매환자에서관찰되는행동심리학적이상행동의근저에는집중력저하가큰역할을함을알수있다. AQS가피질하고신호병변의정도를잘반영하는점을고려하면피질과피질하구조의연결성을반영하는초기지표가될수도있다. K-MMSE, CDR, GDS는인지기능및치매중등도를평가하기위한도구로널리사용되고있지만, K-MMSE 의경우대상환자들의환자의교육, 연령등의인구사회학적변인에영향을많이받으며전두엽기능과같은일부인지기능의변화를반영하는데둔감하다는단점이있다 [17]. CDR도정확한평가를위해서는환자및보호자가모두내원하여야비교적긴문진이필요하다 [18]. 그러나 AQS는환자의내원여부에관계없이보호자에의하여쉽게환자의주의력을평가할수있고의사의문진없이외래진료대기시간에작성될수있다는장점이있다. 본연구에서 AQS는 K-MMSE (γ = 0.371), CDR (γ = ), GDS (γ = ) 등의척도와모두통계적으로유의한상관을보였다 ( 모두 p < 0.001). 또한 AQS와한국어판알츠하이머병-삶의질척도 (Korean Quality of Life-Alzheimer s Disease) 와우수한상관성을보였으며 AQS 점수가저하될수록삶의질점수가낮

6 주의력설문지척도를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 85 아졌다. AQS 점수가높을수록삶의질점수는높아졌다 [19]. 이러한점은 AQS가치매환자의집중력뿐만아니라삶의질을평가하는간접척도로서의가능성을제시한다. 주의력을반영하는 AQS가다른인지기능척도에비하여피질하고신호병변을민감하게반영하는이유는아직확실하지않지만다음의두가지가설로설명할수있다. 첫째, 메이너트핵 (nucleus basalis Mynert) 에서대뇌피질에이르는콜린성신경섬유가피질하백질을따라주행하기때문에피질하고신호병변은콜린성신경섬유묶음의단절을초래하여결과적으로피질- 선조- 시상-피질고리 (cortico-striato-thalamo-cortical circuits) 를파괴하게된다. 결과적으로이러한구조물에위하여매개되는하향조정을통한선택적주의력과지속적주의력에장애를일으키게된다 [20, 21]. 둘째, PWM에는서로멀리떨어진대뇌피질영역을연결하는연관섬유 (association fiber) 들이주로주행하고, DWM에는상대적으로가까운대뇌피질영역을연결하는 U 섬유 (U-fiber) 들이주행한다 [15, 21, 22]. 피질하고신호병변에의한이러한구조물의단절은국소대뇌영역보다는여러대뇌영역의유기적활성화를반영하는주의력에더많은영향을주게된다. 또 AQS가주의력에중점을둔설문지이긴하지만주의력이라는인지기능의특성상일부항목에서다른인지영역을반영하는설문을포함하고있다. 예를들어문항 1, 5, 9, 14, 15는비교적주의력이나집중력에대한직접적인질문내용이지만문항 2, 3, 4는주의력과관련된기억력의일부를, 문항 7 은주의력과관련된시공간능력의일부를, 문항 6, 8, 10, 11, 12, 13은주의력과관련된전두엽기능을반영한다 (Appendix). 따라서 AQS 가주의력을중심으로인지영역들을복합적으로평가하게되므로다른척도에비하여피질하고신호병변을반영하는데민감하게작용하게된것으로생각된다. 이번연구는몇가지제한점을갖는다. 첫째, 피질하허혈로추정되는고신호병변만을대상으로하였고소공경색의유무를반영하지못하였다는점이다. 소공경색은 AD를비롯한여러치매질환의인지기능에부정적인영향을미치므로 [23] 동반된소공경색의유무를반영하는것이필요하다. 아직까지뇌영상만으로소공경색을 Virchow-Robin 공간과구분하여평가할수있는방법론이확립되어있지않았으며 [24] 소공경색의크기, 위치, 형태, 숫자등에따른차이가확립되어있지않아 [7] 소공경색에대한평가를제외하였다. 둘째피질하고신호병변이없는환자를따로분류하지않았다. 본연구의최소피질하고신호병변군은실제로피질하고신호병변이전혀없는집단과경미한피질하고신호병변이동반된집단이혼재된비균질집단이다. 그러나뇌영상에기초한백질고신호측정척도의대부분은본연구에서와마찬가지로일정한기준이하의백질고신호를최소기준으로하여분류하고있다 [25]. 셋째, 피질하허혈의정도이외의다른요소, 즉전두엽위축이나피질하고신호 병변의위치등을고려하지못하였다. 넷째 DWM과 PWM을구분하여평가하지않고 D와 P의조합에의해서만평가하였다는점도제한점이라고본다. 이러한제한점에도불구하고본연구는 AQS가피질하고신호병변의정도를잘반영함을확인하였다. 이러한결과는 AD나 SVD 환자를평가하는임상현장에서 AQS를치매환자의피질하고신호병변정도를반영하는지표로유용할수있다는가능성을제시하고있다. 또 AQS는기존의 MMSE나 CDR, GDS와같은척도와는달리환자없이보호자만내원하여진료받는경우에도많은시간을들이지않고환자의상태를알아볼수있다는장점이있다. 따라서 AQS는기존의치매척도와좋은상관성을갖는집중력평가척도이며환자의내원유무에관계없이보호자에의하여작성될수있고특히피질하고신호병변의정도를반영하는유용한지표가될수있음을확인하였다. 참고문헌 1. Perry RJ, Hodges JR. Attention and executive deficits in Alzheimer s disease. A critical review. Brain 1999; 122: Parasuraman R, Haxby, James V. Attention and brain function in Alzheimer s disease: a review. Neuropsychology 1993; 7: Chan RC. Dysexecutive symptoms among a non-clinical sample: a study with the use of the Dysexecutive Questionnaire. Br J Psychol 2001; 92: Dywan J, Segalowitz SJ. Self- and family ratings of adaptive behavior after traumatic brain injury: psychometric scores and frontally generated ERPs. J Head Trauma Rehabil 1996; 11: Burgess PW, Alderman N, Evans J, Emslie H, Wilson BA. The ecological validity of tests of executive function. J Int Neuropsychol Soc 1998; 4: Ray C, Phillips L, Weir WR. Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention. Br J Clin Psychol 1963; 32: Doddy RS, Massman PJ, Mawad M, Nance M. Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer s disease: comparison to small vessel ischemic vascular dementia. Neuropsychiatry Neuropsychol Behav Neurol 1998; 11: Binetti G, Magni E, Padovani S, Cappa SF, Bianchetti A, Trabucchi M. Excutive dysfunction on early Alzheimer s disease. J Neurol Neurosurg Psychiatry 1996; 60: 91-3.

7 86 구본대 김상윤 9. Kim SY, Park MH, Han SH, Na HR, Cho S, Choi MS, et al. Validation analysis of the attention questionnaire Scale. J Alzheimers Dis 2011; 24: McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer s Disease. Neurology 1984; 34: Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993; 43: Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999: 13: Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HB. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet 2000; 356: Paul RH, Haque O, Gunstad J, Tate DF, Grieve SM, Hoth K, et al. Subcortical hyperintensities impact cognitive function among a select subset of healthy elderly. Arch Clin Neuropsychol 2005; 20: De Groot JC, De Leeuw FE, Oudkerk M, Van Gijn J, Hofman A, Jolles J, et al. Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol 2002; 52: Debette S, Bombois S, Bruandet A, Delbeuck X, Lepoittevin S, Delmaire C, et al. Subcortical hyperintensities are associated with cognitive decline in patients with mild cognitive impairment. Stroke 2007; 38: Kang YW, Na DL, Hahn SH. Validity study on the Korean mini-mental state examination (K-MMSE) in dementia patients J Kor Neurol Assoc 1997; 15: Choi SH, Na DL, Lee BH, Ham DS, Jung JH, Yoon SJ, et al. Estimating the validity of the Korean version of expanded clinical dementia rating (CDR) scale. J Kor Neurol Assoc 2001; 19: Kim HJ, Moon SY, Kim S, Han SH. Assessment of the quality of life in patients with Alzheimer s disease. J Korean Neurol Assoc 2008; 26: Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998; 121: Cummings JL. Frontal-subcortical circuits and human behavior. J Psychosom Res 1998; 44: Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53: Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun study. JAMA 1997; 277: Sasaki M. Pitfalls in the interpretation of central nervous system disorders from structural magnetic resonance images Brain Nerve 2010;62: Bocti C, Swartz RH, Gao FQ, Sahlas DJ, Behl P, Black SE. A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia. Stroke 2005; 36:

8 주의력설문지척도를이용한알츠하이머병과피질하혈관성치매환자의피질하고신호병변에따른주의집중력의차이 87 Appendex. Attention Questionnaire Scale 번호질문점수 1 쉽게산만해집니까? AQS1 (Negative Question) 2 외출시문잠그는것을잊습니까? 집안의물건을못찾아힘들어합니까? 하라고시킨일들을하는데문제가있습니까? 긴대화를할때, 주제에서자주벗어납니까? 사람이많은장소에가면쉽게당황합니까? 익숙한곳에서도길을잃는경우가있습니까? 대화나일상활동중자주졸려하는경우가많습니까? 한가지일에집중을잘합니까? AQS2 (Positive Question) 10 주변에서일어나는일에관심을보입니까? 스스로무언가를하려고합니까? 예전에하던취미생활을계속하고있습니까? 새로운것에대한관심과흥미를보입니까? 식사도중에대화를유지할수있습니까? TV 시청시집중을잘합니까? = 전혀그렇지않다 (never), 1= 가끔또는조금그렇다 (occasionally), 2= 항상또는많이그렇다 (usually). AQS, Attention Questionnaire Scale; AQS1, negative questions which are consisted of AQS No. 1-8; AQS2, positive questions which are consisted of AQS No. 9-15; AQS score =16-AQS1+AQS2.

Dementia2

Dementia2 Today s Topics Memory Impairment & Dementia Age Associated Memory Impairment Dementia Definition of dementia Depression Schizophrenia Mental retardation Delirium : Not final diagnosis term, but symptomatologic